tbuckley/cabot-search huggingface dataset:
Cocoa Extract Supplementation and Risk of Type 2 Diabetes: The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) Randomized Clinical Trial
Authors: Jie Li, Howard D. Sesso, Eunjung Kim, JoAnn E. Manson, Georgina Friedenberg, Allison Clar, Trisha Copeland, Aladdin H. Shadyab, Jean Wactawski-Wende, Lesley Tinker, Simin Liu
Journal: Diabetes Care (2023)

OBJECTIVE Observational studies have indicated that cocoa flavanol supplementation may be a promising strategy for type 2 diabetes (T2D) prevention. We aimed to directly evaluate its clinical efficacy in a large randomized clinical trial (RCT). RESEARCH DESIGN AND METHOD The Cocoa Supplement and Multivitamin Outcomes Study (COMSOS) was a 2 × 2 factorial RCT performed from June 2015 to December 2020 that tested cocoa extract and a multivitamin for the prevention of cardiovascular disease (CVD) and cancer. A total of 21,442 U.S. adults free of CVD and recent cancer, including 12,666 women aged ≥65 years and 8,776 men aged ≥60 years, were randomly assigned to receive cocoa extract [500 mg/day cocoa flavanols, including 80 mg (−)-epicatechin] or placebo. In this study, we included 18,381 participants without diabetes at enrollment and examined the effect of cocoa extract supplementation on incident self-reported T2D in intention-to-treat analyses. RESULTS During a median follow-up of 3.5 years, 801 incident T2D cases were reported. Compared with placebo, taking a cocoa extract supplement did not reduce T2D (adjusted hazard ratio 1.04, 95% CI 0.91–1.20, P = 0.58). Stratification analyses showed that the effect of cocoa extract supplementation was not significantly modified by sex, race, BMI, smoking, physical activity, dietary quality, flavanol status at baseline, or randomized multivitamin assignment. CONCLUSIONS Middle-aged and older adults taking a cocoa extract supplement for a median of 3.5 years did not reduce their risk of incident T2D. Further studies of cocoa extract supplementation beginning earlier in adulthood and in populations with different background diets are warranted.
A commentary on ‘The safety and efficacy between remimazolam and propofol in intravenous anaesthesia of endoscopy operation: a systematic review and meta-analysis’
Authors: Junhong Chen, Hao Zhou, Kai Liu
Journal: International Journal of Surgery (2023)

Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, Changchun, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Department of Hepatobiliary and Pancreatic Surgery II, General Surgery Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, 130021, P.R. China. Tel: +86-13604310551. E-mail address: [email protected] (K. Liu). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Incidence of MACE in Patients Treated With CAR-T Cell Therapy
Authors: Bénédicte Lefebvre, Yu Kang, Azin Vakilpour, Takeshi Onoue, Noelle V. Frey, Priya Brahmbhatt, Brian Huang, Kemi Oladuja, Daniel Koropeckyj-Cox, Courteney Wiredu, Amanda M. Smith, Jesse Chittams, Joseph Carver, Marielle Scherrer-Crosbie
Journal: JACC CardioOncology (2023)

Previous retrospective studies have shown that chimeric antigen receptor T (CAR-T) cell therapy may be associated with major adverse cardiovascular events (MACE), especially in the context of cytokine-release syndrome (CRS) events.
Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors
Authors: Feifei Fang, Yang Dai, Hao Wang, Yinchun Ji, Xuewu Liang, Xia Peng, Jiyuan Li, Yangrong Zhao, Chunpu Li, Danyi Wang, Yazhou Li, Dong Zhang, Dan Zhang, Meiyu Geng, Hong Liu, Jing Ai, Yu Zhou
Journal: Acta Pharmaceutica Sinica B (2023)

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.
From Berlin to Global: The Need for Syndromic Definitions of Acute Respiratory Distress Syndrome
Authors: Narges Alipanah-Lechner, Alexandre B. Cavalcanti, Janet Diaz, Niall D. Ferguson, Sheila N. Myatra, Carolyn S. Calfee
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"From Berlin to Global: The Need for Syndromic Definitions of ARDS." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
The potential of a multimodal digital care program in addressing healthcare inequities in musculoskeletal pain management
Authors: Anabela C. Areias, Maria Molinos, Robert G. Moulder, Dora Janela, Justin K. Scheer, Virgílio Bento, Vijay Yanamadala, Steven P. Cohen, Fernando Dias Correia, Fabíola Costa
Journal: npj Digital Medicine (2023)

Abstract Digital interventions have emerged as a solution for time and geographical barriers, however, their potential to target other social determinants of health is largely unexplored. In this post-hoc analysis, we report the impact of social deprivation on engagement and clinical outcomes after a completely remote multimodal musculoskeletal (MSK) digital care program managed by a culturally-sensitive clinical team. Patients were stratified in five categories according to their social deprivation index, and cross-referenced with their race/ethnicity, rurality and distance to healthcare facilities. From a total of 12,062 patients from all U.S. states, 8569 completed the program. Higher social deprivation was associated with greater baseline disease burden. We observed that all categories reported pain improvements (ranging from −2.0 95%CI −2.1, −1.9 to −2.1 95%CI −2.3, −1.9, p &lt; 0.001) without intergroup differences in mean changes or responder rates (from 59.9% (420/701) to 66.6% (780/1172), p = 0.067), alongside reduction in analgesic consumption. We observed significant improvements in mental health and productivity across all categories, with productivity and non-work-related functional recovery being greater within the most deprived group. Engagement was high but varied slightly across categories. Together these findings highlight the importance of a patient-centered digital care program as a tool to address health inequities in musculoskeletal pain management. The idea of investigating social deprivation within a digital program provides a foundation for future work in this field to identify areas of improvement.
ZNT1 and Zn2+ control TLR4 and PD-L1 endocytosis in macrophages to improve chemotherapy efficacy against liver tumor
Authors: Dan Yang, Taikun Tian, Xiaojing Li, Baokai Zhang, Linlin Qi, Fang Zhang, Mingshun Han, Shuang Wang, Jun Xiao, Yingying Gou, Raorao Zhang, Qiaojie Liu, Sheng Su, Jiahui Liu, Xiaowu Huang, Qiang Gao, Lijian Hui, Huiru Tang, Yuncong Chen, Hongyan Wang, Bin Wei
Journal: Hepatology (2023)

HCC is closely associated with inflammation and immune modulation, and combined chemotherapy with other strategies is under extensive investigation to achieve better efficacy. HCC is accompanied by zinc (Zn) deficiency. This study aims to understand how Zn could affect macrophage function and its application for HCC therapy.
Volumetric tumor tracking from a single cone-beam X-ray projection image enabled by deep learning
Authors: Jingjing Dai, Guoya Dong, Chulong Zhang, Wenfeng He, Lin Liu, Tangsheng Wang, Yuming Jiang, Wei Zhao, Xiang Zhao, Yaoqin Xie, Xiaokun Liang
Journal: Medical Image Analysis (2023)
Early adoption of laparoscopic liver surgery in Poland: a national retrospective cohort study
Authors: Wacław Hołówko, Wojciech Serednicki, Mateusz Bartkowiak, Michał Wysocki, Marian Domurat, Jerzy Mielko, Stanisław Pierściński, Piotr Hogendorf, Łukasz Masior, Piotr Kalinowski, Mateusz Wierdak, Mariusz Frączek, Aleksander Tarasik, Tadeusz Wróblewski, Andrzej Budzyński, Michał Pędziwiatr, Michał Grąt
Journal: International Journal of Surgery (2023)

Background: The need for safe and efficient dissemination of minimally invasive approach in liver surgery is among the current challenges for hepatobiliary surgeons. After the stage of innovators and pioneers, the following countries should adopt a laparoscopic approach. The aim of this study was to assess the national experience and trend in implementing laparoscopic liver resection (LLR) in Poland. Materials and Methods: A national registry of LLR performed in Poland was established in June 2020. All LLR cases performed before were included retrospectively, followed by prospectively collected new cases. Baseline characteristics, preoperative and intraoperative data, short-term results and long-term follow-up were recorded. Results: Since 2010 up to the end of 2022 there were 718 LLRs performed in Poland. The national rate of laparoscopic approach has gradually increased since 2017 ( P &lt;0.001), reaching the rate of 11.7% in 2022. There were 443 (61.7%), 107 (14.9%) and 168 (23.4%) LLRs performed in accordance to increasing grades of difficulty. The move towards more demanding cases had an increasing trend over the years ( P &lt;0.001). Total intraoperative adverse event and postoperative severe complications rates were estimated for 13.5% (n=97) and 6.7% (n=48), respectively. 30-day reoperation, readmission and postoperative mortality rates were 3.6% (n=26), 2.8% (n=20) and 0.8% (n=6), respectively. While the R0 resection margin was assessed in 643 (89.6%) cases, the total textbook outcomes (TO) were achieved in 525 (74.5%) cases. Overcoming the learning curve of 60 LLRs, resulted in an increasing TO rate from 72.3% to 80.6% ( P =0.024). Conclusion: It is the first national analysis of a laparoscopic approach in liver surgery in Poland. An increasing trend of minimizing invasiveness in liver resection has been observed. Responsible selection of cases in accordance with difficulty may provide results within global benchmark values and textbook outcomes already during the learning curve.
Claudin-2 protects against colitis-associated cancer by promoting colitis-associated mucosal healing
Authors: Rizwan Ahmad, Balawant Kumar, Ishwor Thapa, Raju Lama Tamang, Santosh K. Yadav, Mary K. Washington, Geoffrey A. Talmon, Alan S. Yu, Dhundy K. Bastola, Punita Dhawan, Amar B. Singh
Journal: Journal of Clinical Investigation (2023)

Patients with inflammatory bowel disease (IBD) are susceptible to colitis-associated cancer (CAC). Chronic inflammation promotes the risk for CAC. In contrast, mucosal healing predicts improved prognosis in IBD and reduced risk of CAC. However, the molecular integration among colitis, mucosal healing, and CAC remains poorly understood. Claudin-2 (CLDN2) expression is upregulated in IBD; however, its role in CAC is not known. The current study was undertaken to examine the role for CLDN2 in CAC. The AOM/DSS-induced CAC model was used with WT and CLDN2-modified mice. High-throughput expression analyses, murine models of colitis/recovery, chronic colitis, ex vivo crypt culture, and pharmacological manipulations were employed in order to increase our mechanistic understanding. The Cldn2KO mice showed significant inhibition of CAC despite severe colitis compared with WT littermates. Cldn2 loss also resulted in impaired recovery from colitis and increased injury when mice were subjected to intestinal injury by other methods. Mechanistic studies demonstrated a possibly novel role of CLDN2 in promotion of mucosal healing downstream of EGFR signaling and by regulation of Survivin expression. An upregulated CLDN2 expression protected from CAC and associated positively with crypt regeneration and Survivin expression in patients with IBD. We demonstrate a potentially novel role of CLDN2 in promotion of mucosal healing in patients with IBD and thus regulation of vulnerability to colitis severity and CAC, which can be exploited for improved clinical management.
The cancer-immunity cycle: Indication, genotype, and immunotype
Authors: Ira Mellman, Daniel S. Chen, Thomas Powles, Shannon J. Turley
Journal: Immunity (2023)

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes the iterative nature of the response where the killing of tumor cells by T cells initiates subsequent rounds of antigen presentation and T cell stimulation, maintaining active immunity and adapting it to tumor evolution. Any step of the cycle can become rate-limiting, rendering the immune system unable to control tumor growth. Here, we update the cancer-immunity cycle based on the remarkable progress of the past decade. Understanding the mechanism of checkpoint inhibition has evolved, as has our view of dendritic cells in sustaining anti-tumor immunity. We additionally account for the role of the tumor microenvironment in facilitating, not just suppressing, the anti-cancer response, and discuss the importance of considering a tumor's immunological phenotype, the "immunotype". While these new insights add some complexity to the cycle, they also provide new targets for research and therapeutic intervention.
Species-specific FMRP regulation of RACK1 is critical for prenatal cortical development
Authors: Minjie Shen, Carissa L. Sirois, Yu Guo, Meng Li, Qiping Dong, Natasha M. Méndez-Albelo, Yu Gao, Saniya Khullar, Lee Kissel, Soraya O. Sandoval, Natalie E. Wolkoff, Sabrina X. Huang, Zhiyan Xu, Jonathan E. Bryan, Amaya M. Contractor, Tomer Korabelnikov, Ian A. Glass, Dan Doherty, Jon E. Levine, André M.M. Sousa, Qiang Chang, Anita Bhattacharyya, Daifeng Wang, Donna M. Werling, Xinyu Zhao
Journal: Neuron (2023)
Use of Updated COVID-19 Vaccines 2023–2024 Formula for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices — United States, September 2023
Authors: Joanna J. Regan, Danielle L. Moulia, Ruth Link-Gelles, Monica Godfrey, Josephine Mak, Morgan Najdowski, Hannah G. Rosenblum, Melisa M. Shah, Evelyn Twentyman, Sarah Meyer, Georgina Peacock, Natalie Thornburg, Fiona P. Havers, Sharon Saydah, Oliver Brooks, H. Keipp Talbot, Grace M. Lee, Beth P. Bell, Barbara E. Mahon, Matthew F. Daley, Katherine E. Fleming-Dutra, Megan Wallace
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.
Author Correction: Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial
Authors: Jamie E. Chaft, Filiz Oezkan, Mark G. Kris, Paul A. Bunn, Ignacio I. Wistuba, David J. Kwiatkowski, Dwight H. Owen, Yan Tang, Bruce E. Johnson, Jay M. Lee, Gerard Lozanski, Maciej Pietrzak, Michal Seweryn, Woo Yul Byun, Katja Schulze, Alan Nicholas, Ann Johnson, Jessica Grindheim, Stephanie Hilz, David S. Shames, Chris Rivard, Eric Toloza, Eric B. Haura, Ciaran J. McNamee, G. Alexander Patterson, Saiama N. Waqar, Valerie W. Rusch, David P. Carbone, Saiama N. Waqar, Elaine Shum, Misako Nagasaka, Marianna Koczywas, Edward B. Garon, David J. Finley, David R. Camidge, Jennifer W. Carlisle, Justin D. Blasberg
Journal: Nature Medicine (2023)
Evaluation of complete response to azacitidine according to the revised International Working Group 2023 response criteria for higher risk MDS. Does it make a difference in patients’ outcome?
Authors: Anthi Bouchla, Sotirios G. Papageorgiou, Argyris Symeonidis, Ioanna Sakellari, Panagiotis Zikos, Thomas P. Thomopoulos, Eleftheria Hatzimichael, Athanasios Galanopoulos, Nora-Athina Vyniou, Ioannis Kotsianidis, Vasiliki Pappa
Journal: Leukemia (2023)
STING activation in TET2-mutated hematopoietic stem/progenitor cells contributes to the increased self-renewal and neoplastic transformation
Authors: Jiaying Xie, Mengyao Sheng, Shaoqin Rong, Dan Zhou, Chao Wang, Wanling Wu, Jingru Huang, Yue Sun, Yin Wang, Pingyue Chen, Yushuang Wu, Yuanxian Wang, Lan Wang, Bo O. Zhou, Xinxin Huang, Colum P. Walsh, Stefan K. Bohlander, Jian Huang, Xiaoqin Wang, Guo-Liang Xu, Hai Gao, Yuheng Shi
Journal: Leukemia (2023)

Abstract Somatic loss-of-function mutations of the dioxygenase Ten-eleven translocation-2 (TET2) occur frequently in individuals with clonal hematopoiesis (CH) and acute myeloid leukemia (AML). These common hematopoietic disorders can be recapitulated in mouse models. However, the underlying mechanisms by which the deficiency in TET2 promotes these disorders remain unclear. Here we show that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated to mediate the effect of TET2 deficiency in dysregulated hematopoiesis in mouse models. DNA damage arising in Tet2 -deficient hematopoietic stem/progenitor cells (HSPCs) leads to activation of the cGAS-STING pathway which in turn promotes the enhanced self-renewal and development of CH. Notably, both pharmacological inhibition and genetic deletion of STING suppresses Tet2 mutation-induced aberrant hematopoiesis. In patient-derived xenograft (PDX) models, STING inhibition specifically attenuates the proliferation of leukemia cells from TET2-mutated individuals. These observations suggest that the development of CH associated with TET2 mutations is powered through chronic inflammation dependent on the activated cGAS-STING pathway and that STING may represent a potential target for intervention of relevant hematopoietic diseases.
Risk of Major Adverse Cardiovascular Events in Immune-Mediated Inflammatory Disorders on Biologics and Small Molecules: Network Meta-Analysis
Authors: Shivani Shah Mattay, Mohammad Zamani, Dany Saturno, Edward V. Loftus, Matthew A. Ciorba, Andres Yarur, Siddharth Singh, Parakkal Deepak
Journal: Clinical Gastroenterology and Hepatology (2023)
Does clinical research account for diversity in deploying digital health technologies?
Authors: Nathan A. Coss, J. Max Gaitán, Catherine P. Adans-Dester, Jessica Carruthers, Manuel Fanarjian, Caprice Sassano, Solmaz P. Manuel, Eric Perakslis
Journal: npj Digital Medicine (2023)

Abstract Digital health technologies (DHTs) should expand access to clinical research to represent the social determinants of health (SDoH) across the population. The frequency of reporting participant SDoH data in clinical publications is low and is not known for studies that utilize DHTs. We evaluated representation of 11 SDoH domains in 126 DHT-enabled clinical research publications and proposed a framework under which these domains could be captured and subsequently reported in future studies. Sex, Race, and Education were most frequently reported (in 94.4%, 27.8%, and 20.6% of publications, respectively). The remaining 8 domains were reported in fewer than 10% of publications. Medical codes were identified that map to each of the proposed SDoH domains and the resulting resource is suggested to highlight that existing infrastructure could be used to capture SDoH data. An opportunity exists to increase reporting on the representation of SDoH among participants to encourage equitable and inclusive research progress through DHT-enabled clinical studies.
Impose of KNDy/GnRH neural circuit in PCOS, ageing, cancer and Alzheimer’s disease: StAR actions in prevention of neuroendocrine dysfunction
Authors: Siva Prasad Panda, Adarsh Kesharwani, Gaurav Deep Singh, DSNBK Prasanth, Bhaskara Raju Vatchavai, P.V. Kamala Kumari, Sunil Kumar Panda, Sarada Prasanna Mallick
Journal: Ageing Research Reviews (2023)
Remodeling the tumor immune microenvironment via siRNA therapy for precision cancer treatment
Authors: Lingxi Jiang, Yao Qi, Lei Yang, Yangbao Miao, Weiming Ren, Hongmei Liu, Yi Huang, Shan Huang, Shiyin Chen, Yi Shi, Lulu Cai
Journal: Asian Journal of Pharmaceutical Sciences (2023)

How to effectively transform the pro-oncogenic tumor microenvironments (TME) surrounding a tumor into an anti-tumoral never fails to attract people to study. Small interfering RNA (siRNA) is considered one of the most noteworthy research directions that can regulate gene expression following a process known as RNA interference (RNAi). The research about siRNA delivery targeting tumor cells and TME has been on the rise in recent years. Using siRNA drugs to silence critical proteins in TME was one of the most efficient solutions. However, the manufacture of a siRNA delivery system faces three major obstacles, i.e., appropriate cargo protection, accurately targeted delivery, and site-specific cargo release. In the following review, we summarized the pharmacological actions of siRNA drugs in remolding TME. In addition, the delivery strategies of siRNA drugs and combination therapy with siRNA drugs to remodel TME are thoroughly discussed. In the meanwhile, the most recent advancements in the development of all clinically investigated and commercialized siRNA delivery technologies are also presented. Ultimately, we propose that nanoparticle drug delivery siRNA may be the future research focus of oncogene therapy. This summary offers a thorough analysis and roadmap for general readers working in the field.